tbuckley/cabot-search huggingface dataset:
Increasing targeted therapy options for patients with relapsed cancer with broader somatic gene panel analysis from the primary tumor: The Profiler02 randomized phase II trial.
Authors: Olivier Tredan, Damien Pouessel, Nicolas Penel, Sylvie Chabaud, Carlos A. Gomez-Roca, Diane Pannier, Mehdi Brahmi, Michel Fabbro, Marie-Eve Garcia, Delphine Larrieu-Ciron, Isabelle Laure Ray-Coquard, Marie Viala, Antoine Italiano, Philippe Alexandre Cassier, Armelle Dufresne, Valéry Attignon, Isabelle Treilleux, Alain Viari, David Pérol, Jean-Yves Blay
Journal: Journal of Clinical Oncology (2022)

3130 Background: PROFILER-02 is a multicenter randomized prospective study comparing the proportion of metastatic cancer patients (pts) with Targeted Agent (TA) recommendation provided by large NGS panel (FOne panel, 324 genes) vs home 87-gene NGS panel (CTRL) (PMID 30865223). Methods: Adult pts with advanced/metastatic cancer during 1 st or 2 nd line of therapy without known targetable gene alteration were eligible and randomized (1:1) to FOne vs CTRL panel. Both panels were performed for each patient. The randomization arm defined the first panel reviewed by dedicated Molecular Tumor Board (MTB) at disease progression while the 2 nd panel remained blinded. The primary objective was the pts rate with at least one TA recommendation by the MTB using either FOne or CTRL panel. The study was designed in order to detect difference in proportions of 10% between the two panels. A sample size of 289 pts with both panels were requested to show this difference with an expected proportion of discordant pairs of 20% using a McNemar's test with 98% power and 5% two-sided significance level. Secondary endpoints included number of pts receiving at least one TA, progression free survival (PFS) and overall survival (OS). Results: From June 2017 to June 2019, among the 339 included pts 171 and 168 pts were randomized in FOne or CTRL panels’ first use, respectively. Median age was 57 years [19.0 - 85.0]; 54.9% were female. The median time from randomization to first MTB was 7.62 months [range 0.80 - 48.1]. Among the 339 pts, 147 pts (43.4%) had no TA recommendation, 108 pts (31.9%) had at least one TA recommendation according to both panels, 67 pts (19.8%) had one or more TA recommendation according to FOne panel only and 17 pts (5%) according to CTRL panel only (McNemar p &lt; 0.001). At the time of the analysis, 51/339 (15%) pts started recommended treatment: 27 pts (8%) with TA recommendation from both panels, 21 pts (6.2%) from FOne only and 3 pts (0.3%) from CTRL only. Main initiated TA were PARP inh. (FOne n = 12; CTRL n = 9), PI3K/AKT/mTOR inh. (FOne n = 10; CTRL n = 9) and immunotherapy (ICI) (FOne n = 7; CTRL n = 0). Median PFS following first MTB were 3.2 months (95% CI 2.5-3.8) and 2.6 months (95% CI 2.0-3.8), median OS were 8.7 months (95% CI 6.6-10.8) and 8.4 months (95% CI 6.4-9.7), in the FOne and CTRL arm, respectively. Conclusions: Larger NGS panel including Tumor Mutational Burden increased the number of recommended options (TA and ICI), as well as the number of treatment initiation. Clinical trial information: NCT03163732.
Clinical and pathological predictors of micrometastasis in marginal thickness melanoma.
Authors: Marita Yaghi, Nadeem Bilani, Barbara Dominguez, Iktej Singh Jabbal, Carlos Rivera, Hong Liang, Paul X Benedetto, Chebli Mrad, Zeina A. Nahleh, Rafael Arteta-Bulos
Journal: Journal of Clinical Oncology (2022)

e21585 Background: Sentinel lymph node biopsy (SLNB) remains controversial in patients with localized marginal thickness melanoma (MTM). Nonetheless, micrometastasis (miLN) i.e. the presence of clinically occult lymph node (LN) metastasis, upstages localized tumors to Stage III, indicating the need for more extensive surgical resection and escalated systemic therapy. We aim to identify disease predictors associated with miLN in MTM. Methods: This National Cancer Database (2004-2018) analysis includes patients with T1a/T1b, N0, and M0 (AJCC 8 th edition) melanoma (Breslow’s depth: 0.76-1.00 mm). We selected 2 cohorts based on the pathological status of LN metastasis, as per SLNB or elective lymphadenectomy: negative LN versus miLN. Bivariate association of various clinical characteristics and LN status was assessed using Chi-square and Fisher’s exact tests. Significant covariates were integrated into a multivariable logistic regression (MLR) with a backward elimination model to identify the risk factors associated with the presence of miLN. A multivariable Cox regression model with backward elimination compared overall survivor (OS) between both cohorts, adjusting for significantly unbalanced factors. Results: N = 72,945 patients with clinical N0 MTM were identified. N = 68,912 (94.5%) had negative LN and N = 4,033 (5.5%) had miLN on pathology. Ethnicity (p = 0.260), Charlson/Deyo comorbidity score (p = 0.0894) and LDH levels (p = 0.2278) did not significantly vary across cohorts. On MLR analysis, patients with miLN were more likely to be younger and have tumors located outside the head &amp; neck. Tumors with miLN were more likely to show lymphovascular invasion, vertical growth, and a mitotic rate of ≥ 1 but less likely to show positive tumor regression. Ulceration was not an independent risk factor of miLN (p = 0.9305). Multivariable analysis showed that patients with miLN had lower OS rates than those with negative LN (HR = 1.66; 95% CI: 1.45-1.90; p &lt; 0.0001). Conclusions: miLN is associated with a worse prognosis, warranting early recognition and prompt treatment initiation. Despite NCCN guidelines incorporating tumor ulceration into decision-making regarding the need for SLNB in clinical N0 MTM, we show that tumor ulceration was not significantly associated with miLN in MTM. However, patient age, tumor location, tumor mitotic rate, lymphovascular invasion, and vertical growth phase were associated with miLN and thus need to be assessed when considering SLNB.[Table: see text]
Improvements in myeloma specific survival over the last two decades.
Authors: Nidhi Mankan, Ajay K. Nooka
Journal: Journal of Clinical Oncology (2022)

e18503 Background: Improvement in overall survival (OS) have been observed among myeloma patients over the last several decades, mainly due to improvement in therapeutic options. For a disease, more common in the elderly (median age of diagnosis of 70), and a median reported OS exceeding 10 years (Joseph et al JCO 2020), reaching normal life-expectancy for a myeloma patient has become more realistic now than ever before. In this context, where the competing risks for mortality for myeloma patients are higher, we have evaluated the changes in the myeloma specific survival (MSS) using a population-based database Surveillance, Epidemiology, and End Results (SEER)-18 database. Methods: Interrogation for International Classification of Diseases (ICD) for Oncology 3rd edition histology codes 9731/3 resulted in 65848 cases. After excluding 1360 cases of extraosseous plasmacytoma and 2011 cases of solitary plasmacytoma of bone, a total of 62477 cases of myeloma were found. 9322 cases were excluded due to myeloma not being the primary malignancy, leaving a total of 53155 cases with active follow for the primary analysis. OS and MSS were estimated using the Kaplan-Meier method. Improvements in OS and MSS were compared by 4 eras (1975-88; 1989-1998; 1999-2008; 2009-2018) by race and gender. Results: White patients (40040 -75.3%) and males (28104 -52.9%) comprised majority of the study population. 9495 black patients (17.9%) and 3004 Asian/Pacific Islanders (5.7%) were the other major racial groups included in the analysis. The median OS for myeloma patients in the era 1975-1988 was 24 months (95% CI 23.22-24.77) while the simultaneous median MSS was 32 months (95% CI 31-32.99). Significant improvements in OS occurred by the era of 2008-2018 (56 months (95% CI 54.31-57.69). Improvement in MSS was more prominently observed during this era - 87 months (95% CI 83.2-90.80). The OS and MSS for each of the groups by gender and race have been tabulated in table. Conclusions: OS and MSS have improved over the last two decades, more prominently in the last decade. Improvement in MSS clearly highlights the fact that myeloma as the primary cause of death has declined over the last two decades among most groups of patients and it is encouraging to see the benefit extending to the minorities. Future studies may incorporate MSS as an endpoint, which might accurately reflect the benefit offered by the newer safer therapeutics.
Risk Factors and Racial and Ethnic Disparities in Patients With Breast Cancer–Related Lymphedema
Authors: Giacomo Montagna, Jennifer Zhang, Varadan Sevilimedu, Jillian Charyn, Kelly Abbate, Ethan A. Gomez, Babak Mehrara, Monica Morrow, Andrea V. Barrio
Journal: JAMA Oncology (2022)

Risk factors for breast cancer-related lymphedema (BCRL) after axillary lymph node dissection (ALND) are poorly understood.To evaluate rates of and risk factors associated with BCRL in a prospective cohort of women treated with ALND.This prospective BCRL screening study performed at a tertiary cancer center enrolled women with breast cancer 18 years and older undergoing breast surgery and unilateral ALND in the primary setting or after sentinel lymph node biopsy.Risk of BCRL during the first 2 years after ALND and radiotherapy.Patients were prospectively evaluated with arm volume (perometer) measurements, and BCRL was defined as a relative volume change of 10% or greater from baseline. Cumulative incidence of BCRL was assessed using competing risk analysis. Risk factors for BCRL were assessed on univariate and multivariable analyses.From November 2016 to March 2020, 304 patients were enrolled; 276 had at least 1 longitudinal measurement. Median (IQR) age was 48 (40-57) years; median (IQR) body mass index, calculated as weight in kilograms divided by height in meters squared, was 26.4 (22.5-31.2). Of the 276 patients included in the analysis, 29 (11%) self-identified as Asian, 55 (20%) as Black, 16 (6%) as Hispanic, 166 (60%) as White, and 10 (3%) as unknown race and ethnicity; 70% received neoadjuvant chemotherapy (NAC); 93% received nodal irradiation. The 24-month BCRL rate was 23.8% (95% CI, 17.9%-29.8%), with significant variation by race and ethnicity (24-month rate: 37.2% [Black], 27.7% [Hispanic], 22.5% [Asian], and 19.8% [White]; P = .004). The BCRL rates were also higher among patients receiving NAC vs up-front surgery (24-month rate: 29.3% vs 11.1%; P = .01). On multivariable analysis, Black race and Hispanic ethnicity (compared with White race) (odds ratio [OR], 3.88; 95% CI, 2.14-7.08 and OR, 3.01; 95% CI, 1.10-7.62, respectively; P < .001 for each), receipt of NAC (compared with up-front surgery) (OR, 2.10; 95% CI, 1.16-3.95; P = .01), older age (OR, 1.04; 95% CI, 1.02-1.07 per 1-year increase; P = .001), and a longer follow-up interval (OR, 1.57; 95% CI, 1.30-1.90 per 6-month increase; P < .001) were independently associated with an increased risk of BCRL, while ERBB2-positive subtype was associated with a decreased risk of BCRL (compared with hormone receptor positive/ERBB2 negative): OR, 0.50; 95% CI, 0.23-0.99; P = .04).In this cohort study, Black race, Hispanic ethnicity, NAC receipt, older age, and longer follow-up were independently associated with risk of BCRL. Studies are warranted to evaluate the biologic mechanisms behind racial and ethnic disparities in BCRL development and alternatives to NAC to avoid ALND in tumor subtypes unlikely to achieve nodal pathologic complete response.
Predictive factors for successful growth of patient derived xenografts (PDX).
Authors: Tatiana Hernandez-Guerrero, Bernard Doger, Jesus Garcia-Foncillas, Michael Jude Wick, Victor Moreno
Journal: Journal of Clinical Oncology (2022)

e15069 Background: PDXs have become a core component of translational cancer research. Developing these models can become challenging since little is known about which factors influence engraftment rates. We sought to determine which clinical, pathological, or molecular factors may predict better engraftment rates in PDXs. Methods: Between March 2017 and January 2021, biopsies obtained from patients with primary or metastatic cancer were implanted into athymic nude mice. Statistical analyses were performed to identify factors that could correlate with final engraftment defined as achievement of at least three passes and sampling of PDXs tumors. We focused on clinical (patient factors) pathological (patients’ tumor samples) and molecular characteristics (patients’ tumor samples) analyzed either by immunohistochemistry (IHC) or next generation sequencing (NGS). Results: 585 tumor samples were collected and implanted. 21 failed to engraft due lack of malignant cells. Of 564 tumor-positive samples, 187 (33.2%) PDXs achieved successful growth at time of analysis (Feb, 21). The following clinical characteristics were correlated with engraftment: systemic antibiotics within 2 weeks of sampling: (38.1% (72/117) antibiotics- group vs 30.7% (115/260) no-antibiotics) (p = 0.048); systemic steroids within 2 weeks (41.5% (34/48) the steroids-receiving group vs 31.7% (153/329) no-steroids) (p: 0.05). For women, menopausal status was predictive: 34.9% (95/177) in postmenopausal achieved growth, Vs 20,4% (10/39) for premenopausal (p = 0.031). Baseline LDH levels: 74.9% (140/187) LDH levels above the upper limit of normality (ULN) against 25.1% (47/187) with normal LDH (p = 0.034). Tumor grade: Grade 1: 25.4% (47/187); grade 2: 34.8% (65/187) and grade 3: 40.1% (75/187) tumors achieved successful growth (p = 0.043). Similarly, higher ki67 levels were also correlated with better engraftment rates: (low (Ki67 &lt; 15%): 8.9% (9/45) achieved growth, Vs high (Ki67 &gt; 15%): 31% (35/113) (p:0.002). Presence of lymphovascular invasion in tumor sample was also predictive: 42.2% (97/230) with lymphovascular Vs 26.9% (90/334) of samples with no invasion (p = 0.0001). Likewise, 41.8% (59/141) of neural invasion-positive samples achieved growth against 30.3% (128/428) (p = 0.008). Mismatch repair deficient tumors showed better engraftment rates: 62.1% (18/29) achieved growth vs 40.8% (75/184) of proficient tumors (p = 0.026). 84 PDX were breast models, among which 57.9% (11/19) ER negative models grew, Vs 15.4% (10/65) of ER positive models (p = 0.0001). Conclusions: tumors with higher grade and Ki67, lymphovascular and/or perineural invasion, with dMMR and ER expression negative have higher chance of PDX development. Some clinical characteristics can also interfere with PDXs development such as use of steroids or antibiotics prior sampling.
LINC-12. Encouraging early outcomes with image guided pencil beam proton therapy for cranio-spinal irradiation and unique considerations for paediatric population – First report from India
Authors: Utpal Gaikwad, Rishan Thimma Sudarsan, M P Noufal, Sylvia Jacinthlyn, Ashok K Reddy, Pankaj Kumar Panda, Srinivas Chilukuri, Dayananda Sharma, Rakesh Jalali
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: To report our experience with image guided pencil beam proton beam therapy (PBT) for craniospinal irradiation (CSI). MATERIALS AND METHODS: Between January 2019 to Dec 2021, we carried out a detailed audit of the first forty patients treated with PBT. All patients were carefully selected after approval from our institutional multidisciplinary tumour and proton board meetings. Median age of the patient cohort was 8 years, and histologies include 20 medulloblastoma, 7 recurrent ependymoma, 3 pineoblastoma, 3 were germ cell tumors and remaining 7 constituted other diagnoses. Forty percent patients received concurrent chemotherapy. We had recorded acute toxicities on a prospectively maintained database. We also report early outcomes in this cohort and discuss limitations of current contouring guidelines during CSI PBT planning. RESULTS: Median CSI dose was 23.4 GyE (Gray Equivalent; range 21.6 - 35). Thirty-five patients (87.5%) completed their CSI without interruption as an outpatient procedure. Five patients required hospital admission during treatment, while one developed grade 3 mucosal toxicity, requiring plan adaptation and treatment break. No patient had grade 2 or more weight loss during the treatment. Forty-five percent (18) developed grade 1 hematological toxicities and 20% (8) developed grade 2 or 3 toxicities; none had grade 4 toxicities. At median follow up of 12 months, 90 % patients are alive of whom 88.9 % are having local control. Special consideration with modification in standard contouring used at our institute helped in limiting acute toxicities in paediatric CSI patients. CONCLUSION: Our preliminary experience with modern contemporary PBT using pencil beam technology and daily image guidance in a range of tumours suitable for CSI is encouraging. Patients tolerated the treatment well with acceptable acute toxicity and expected short-term survival outcome. In paediatric CSI patients, modification in standard contouring guidelines required to achieve better results with PBT
Phase 1 study of SGN-B7H4V, a novel, investigational vedotin antibody–drug conjugate directed to B7-H4, in patients with advanced solid tumors (SGNB7H4V-001, trial in progress).
Authors: Amita Patnaik, Nehal J. Lakhani, Ping Xu, Natalya N. Nazarenko, Justin A Call
Journal: Journal of Clinical Oncology (2022)

TPS3155 Background: B7-H4, a B7 immune checkpoint ligand, is expressed at low levels in normal tissue and negatively regulates T-cell function by inhibiting T-cell proliferation and cytokine production. B7-H4 expression is elevated in solid tumors, including breast, ovarian, and endometrial cancers. Targeting B7-H4–expressing tumor cells may relieve B7-H4–mediated T-cell inhibition. SGN-B7H4V is a novel, investigational vedotin antibody–drug conjugate directed to B7-H4 with proposed mechanisms of action including monomethyl auristatin E (MMAE)-directed cytotoxicity, bystander effect, antibody-dependent cellular cytotoxicity, and antibody-dependent cellular phagocytosis. SGN-B7H4V elicited antitumor activity in cell line-derived xenograft models of triple-negative breast cancer (TNBC) and patient-derived xenograft models of TNBC and ovarian cancer (Gray et al 2021), providing a rationale to evaluate SGN-B7H4V in patients (pts) with advanced solid tumors. Methods: SGNB7H4V-001 (NCT05194072) is a phase 1, first-in-human, multicenter, open-label trial evaluating the safety, tolerability, pharmacokinetics (PK), and antitumor activity of SGN-B7H4V in pts with advanced solid tumors. This study includes 3 parts: dose escalation (Part A), dose and schedule optimization (Part B), and dose expansion in disease-specific cohorts and a biology cohort (Part C). Adult pts (≥18 years) with histologically/cytologically confirmed locally advanced unresectable or metastatic solid tumors including high-grade serous epithelial ovarian cancer, primary peritoneal cancer, fallopian tube cancer, human epidermal growth factor receptor 2-negative and hormone receptor-positive breast cancer, TNBC, endometrial carcinoma, squamous non-small cell lung cancer, cholangiocarcinoma, or gallbladder carcinoma, are eligible. Pts must have ECOG PS 0–1 and relapsed/refractory disease or be intolerant to standard-of-care therapies. Prior treatment with an MMAE-containing agent or a B7-H4–targeted agent is not permitted. Primary endpoints include the rate of adverse events, laboratory abnormalities, dose-limiting toxicities, and cumulative dose-level safety. Secondary endpoints are objective response rate (ORR), complete response rate, duration of objective response (DOR), progression-free survival (PFS), overall survival (OS), PK, and incidence of antidrug antibodies. Exploratory endpoints include pharmacodynamic (PD) analyses, PD and PK exposure measurements, B7-H4 characterization on malignant cells, and biomarker analyses. Safety and antitumor activity endpoints will be assessed using descriptive statistics. ORR will be analyzed by tumor type and dose. DOR, PFS, and OS will be estimated using the Kaplan–Meier method. Enrollment for Part A is ongoing in North America and is planned in Europe. Clinical trial information: NCT05194072.
The optimal dissemination of scientific manuscripts via social media: A prospective randomized trial comparing visual abstracts with key figures using consecutive original manuscripts published in European Urology
Authors: Z. Klaassen, E. Vertosick, A.J. Vickers, M.J. Assel, G. Novara, C. Pierce, C.J.D. Wallis, A. Larcher, M.R. Cooperberg, J.W.F. Catto, A. Kutikov
Journal: European Urology (2022)
Physical and psychological symptom burden in patients newly diagnosed with solid organ cancers in a tertiary care centre in India.
Authors: Atul Batra, akash kumar, Raja Pramanik, Sachin Khurana, Deepam Pushpam, Sameer Bakhshi, Atul Sharma, Ajay Gogia, Prabhat Singh Malik
Journal: Journal of Clinical Oncology (2022)

e24081 Background: Assessment of physical and psychological symptoms using patient-reported outcome (PRO) scales is an often overlooked aspect in oncological practice in resource constrained settings. We assessed the pattern of symptoms at diagnosis in solid organ cancers using an innovative smart device based delivery of the Edmonton Symptom Assessment Scale (ESAS). Methods: We assessed PROs using ESAS at diagnosis in adult patients diagnosed with solid organ cancers at a large tertiary care centre in New Delhi, India from September 2021 to January 2022. The ESAS was delivered to patient's smart phone as a text message that provided a unique link to complete the questionnaire in Hindi or English, as preferred by the patient. Symptom severity was categorized into physical, psychological, and total symptom domains and the scores were further classified as none to mild (0-3) or moderate to severe (4-10). Univariate and Multivariate logistic regression analyses were performed to determine predictive factors. Results: Text message with ESAS completion link was sent to 653 consecutive patients, of whom 509 (77.9%) completed the questionnaire during the study period. The median age was 52 years and 53.2 % were males. The primary cancer site was lung, breast, gastrointestinal, and others in 27.7%, 28.1%, 14.4%, and 29.8%, respectively. Pain (59.1%) and tiredness (57.8%) constituted the maximum physical symptom scores in moderate and severe category. Patients with lung cancer had most physical symptoms categorised in moderate and severe compared with other cancers (P = 0.03), while psychological symptoms were more likely to be moderate to severe females (P = 0.01). In the multivariable logistic regression analysis after adjusting for measured confounders, primary cancer site (lung vs others) and sex (female vs male) were significant predictors for moderate and severe physical and psychological symptoms, respectively. Conclusions: A simple mobile-based ESAS delivery system can help in collecting PRO data to assess symptom burden in patients diagnosed with cancer. The symptom burden assessment can aid in providing personalised symptom-directed measures to improve the quality of life of patients with cancer.
Pentraxin-3: A novel serum biomarker to predict the risk of prostate cancer in patients submitted to prostate biopsy
Authors: G.M. Busetto, U.G. Falagario, G.S. Netti, O. Selvaggio, F. Sanguedolce, E. Ranieri, C. Bettocchi, G. Carrieri, L. Cormio
Journal: European Urology (2022)